Calcium Binding and Transport by Coenzyme Q

Abstract

Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV–vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography–mass spectrometry (HPLC–MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca2+ across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca2+ and redox homeostasis.

Ubiquinone-10 in gold-immobilized lipid membrane structures acts as a sensor for acetylcholine and other tetraalkylammonium cations

“…The actual structure of the ion-pair and the way in which TBA + is coupled to the UQ  anion radical is unclear and out of the scope of this report. However, the formation of UQ-Cation complexes has been reported before and it is therefore not unlikely that a similar process may occur in the described system [11].…”

“…Other studies have suggested that UQ in the cell membrane may be involved in the function of sodium pumps in E. Coli and K. pneumoniae [7; 8], although this claim has been questioned [9; 10]. Recent reports have found that UQ may be involved in redox homeostasis and act as a regulator of calcium cations in mitochondria [11]. Furthermore, studies with membrane anchored quinones have shown that these molecules can drive the transfer of divalent cations (calcium, barium, strontium and magnesium) across biomimetic membranes [12].…”

“…Due to its high lipophilicity and well studied electrochemical behaviour in lipophilic environments in contact with water, UQ has been used to mediate electron, proton and ion transfer reactions on electrodes modified with biomimetic membranes (examples found in references [11,15,21]). The obtained results have provided with a clearer picture regarding the role of UQ in cell membranes.…”

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

“…Although the number of studies related to the chemical and redox features of CoQ family members has increased tremendously in the last three decades [8][9][10][11][12][13][14][15][16][17][18], many key features are still not well understood. In our last two publications we have shown that Coenzyme Q-1 (CoQ-1) and CoQ-10 undergo structural changes in strong alkaline environment or in the presence of Cytochrome P450 enzymes [19,20]. As main reaction products we identified several hydroxy derivatives of CoQ-1 and CoQ-10 [19,20].…”

“…In our last two publications we have shown that Coenzyme Q-1 (CoQ-1) and CoQ-10 undergo structural changes in strong alkaline environment or in the presence of Cytochrome P450 enzymes [19,20]. As main reaction products we identified several hydroxy derivatives of CoQ-1 and CoQ-10 [19,20]. The "isoprenoid Q and HQ" mainly function as electron and proton carriers [4][5][6][7], but it was not until recently that new properties of the hydroxy derivatives of CoQ-1 and CoQ-10 were unraveled highlighting their potential for binding earth-alkaline cations and even facilitating their transfer across biomimetic membranes [19,20].…”